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Cells that Speed up Organ Growth…Also Speed Up Aging

More than two thousand years ago, Greek philosopher Aristotle observed that larger animals tend to live longer than smaller ones. However, today, in the journal Developmental Cell,scientists report that it is cell size—not body size—that affects lifespan. Researchers in Israel, Canada, and Germany examined the pancreases of 24 mammalian species—from the smallest (shrew) to the tallest (giraffe)—and found that animals with larger pancreatic cells tend to age faster, while those with smaller cells seem to live longer.

“A correlation between two things that are so remote was shockingly beautiful and unexpected,” says senior author Dr. Yuval Dor, who studies developmental biology at The Hebrew University’s Hadassah Medical School in Jerusalem.

Previously, scientists had thought that after birth, most mammals’ organs, including the pancreas, grow by cell proliferation. However, Dor and his colleagues made a serendipitous observation: they needed a higher magnification to look at pancreatic cells of new-born mice through a microscope than they did to look at those of adults, suggesting that each cell’s volume was substantially increasing from infant to adult life.

Repeated measurements showed that the growth of individual exocrine pancreatic cells, known as acinar cells, is responsible for much of organ growth after birth. “This was surprising because the assumption was that post-natally, the pancreas grows by increasing the number of cells, just as most organs do,” said Dor.

But when the researchers looked at the same cell type in humans, they realized that cell replication—not individual cell expansion—was solely responsible for pancreatic growth. This got them curious, so they ventured to neighboring labs, at the Jerusalem Biblical Zoo and Kimron Veterinary Institute. There they examined pancreases from a variety of mammals, from tiny Etruscan shrews to tigers.

Upon analyzing the data, the scientists found a strong negative correlation between the size of individual acinar cells and lifespan. Mammalian species that aged faster had larger acinar cells, whereas species that lived longer had smaller acinar cells.

To explain the correlation, the researchers focused in on the underlying molecular mechanism. Their prime suspect is mTOR, a protein that functions at the junction between cell size and lifespan.

“Our working hypothesis is that mTOR activity gives mammals an advantage in early life, possibly by allowing faster growth and a shorter time to sexual maturity and reproduction. However, mTOR also drives deterioration and aging later in life,” Dor shared. “This might explain why some mammal species sacrifice longevity for the rapid early organ growth associated with cell growth instead of replication: you get the selective advantage in early life but you pay the price later on,” Dor added.

This study gives a molecular “face” to the evolutionary theory of aging called antagonistic pleiotropy. The theory suggests that aging is the unintended consequence of mechanisms that are advantageous during reproduction age. More experiments are needed to test this hypothesis, concluded Dor.